Evaluation of antiandrogen therapy in unresectable hepatocellular carcinoma: results of a European Organization for Research and Treatment of Cancer multicentric double-blind trial.
OBJECTIVE
The aim of the study was to evaluate the efficacy of antiandrogen therapy on overall survival and response in unresectable hepatocellular carcinoma (HCC).


METHODS
A total of 244 patients with unresectable HCC were included in this multicentric double-blind trial. According to a two-by-two factorial design, patients were randomly assigned to receive one of the following treatments: pure antiandrogen plus placebo (A+P group, 60 patients); luteinizing hormone-releasing hormone (LHRH) agonist plus placebo (LHRH+P group, 62 patients); pure antiandrogen plus LHRH agonist (A+LHRH group, 62 patients); or placebo plus placebo (P+P group, 60 patients). Pure antiandrogen consisted of Anandron (Roussel-Uclaf Laboratory, Romainville, France) administered orally (300 mg daily for 1 month, then 150 mg daily). LHRH consisted of goseriline acetate (3.6 mg) or triptoreline (3.75 mg) administered monthly by subcutaneous injection. Treatment was given until death. Response was evaluated every 8 weeks according to World Health Organization (WHO) criteria.


RESULTS
Six patients were considered ineligible. One patient had a complete response (A+P arm) and three had a partial response (two in the LHRH+P arm and one in the A+LHRH arm). An overall log-rank test did not demonstrate any significant difference in survival among the four arms. Taking the factorial design into account, comparison of survival showed no significant difference between Anandron-containing regimens and others, or between LHRH-containing regimens and others. No serious side effects occurred for any regimen.


CONCLUSIONS
This controlled study shows clearly the lack of efficacy of androgen treatment in unresectable HCC.
Grimaldi
C
C
Hôpital de Cimiez, Nice, France.
Bleiberg
H
H
Gay
F
F
Messner
M
M
Rougier
P
P
Kok
T C
TC
Cirera
L
L
Cervantes
A
A
De Greve
J
J
Paillot
B
B
Buset
M
M
Nitti
D
D
Sahmoud
T
T
Duez
N
N
Wils
J
J
D000726:Androgen Antagonists / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D015996:Survival Rate; D017329:Triptorelin Pamoate / Q000627:therapeutic use
D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D007093:Imidazoles; D048289:Imidazolidines; D017329:Triptorelin Pamoate; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; C021277:nilutamide